|Publication number||US5577137 A|
|Application number||US 08/392,152|
|Publication date||Nov 19, 1996|
|Filing date||Feb 22, 1995|
|Priority date||Feb 22, 1995|
|Publication number||08392152, 392152, US 5577137 A, US 5577137A, US-A-5577137, US5577137 A, US5577137A|
|Inventors||Howard P. Groger, Peter Lo, Russell J. Churchill, Martin Weiss, Shufang Luo|
|Original Assignee||American Research Corporation Of Virginia|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (36), Non-Patent Citations (16), Referenced by (99), Classifications (25), Legal Events (4)|
|External Links: USPTO, USPTO Assignment, Espacenet|
This invention relates to fluorescent sensors for chemical analysis.
Optical sensors are used in the determination of the chemical properties of liquid or gas-phase analytes. Existing sensors typically place the sensor material either in the evanescent field of the waveguide or at the tip of an optical fiber. The sensitivity of sensors based on evanescent field excitation is limited by the quantity of fluorescence coupled to the waveguide or fiber structure. The total quantity of fluorescence collected at a photodetector is also limited by inefficiencies associated with coupling light from the source to the optical waveguide or optical fiber. The specificity of fluorescent chemical sensors is limited by interferences associated with chemical reactions between the sensor material and materials other than the analyte.
Needs exist for optical waveguide sensors that can increase specificity, sensitivity and precision of fluorescent chemical sensors.
The present invention relates to optical sensors for identifying and measuring concentrations of chemical analytes in either gaseous or liquid phase. The invention provides optical instruments for chemical and biochemical analysis of materials, gases and liquids. The instruments are used for chemical detection of toxic or hazardous materials, in environmental monitoring, and for evaluating process conditions in chemical processing, food processing, or pharmaceutical manufacturing operations. Other applications are in pollution exhaust monitoring in the energy conversion industry, solvent monitoring in distillation processes, and in biomedical analyses.
A sensor according to the invention is used in measuring concentrations of gaseous pollutants, toxic chemicals or materials important in chemical process operations located in the vicinity of the sensor. The present invention relies for its operation on changes in fluorescence emitted from fluorophores either incorporated in optical waveguides or deposited on optical waveguides resulting from exposure of the fluorophores to analytes of interest.
The specificity of optical chemical sensors is limited because of the wide range of chemical reactions between sensor materials and materials other than the analyte of interest. The present invention addresses that problem through the formation of a vector quantity based on the response of several fluorescent sensors, each sensor having a different sensor material or host material. The total response, given in terms of a chemometric measure of each of the fluorophore responses, is specific for a particular analyte and allows for calibration of the instrument during operation. In situ calibration during sensor operation in turn improves the accuracy of the instrument in each measurement.
The present invention uses a light source, which may be a laser, a light-emitting diode or any other modulatable lamp or illumination device, to excite fluorescence in a sensor material incorporated either in an optical waveguide structure or in a coating on a waveguide structure. The key to the achievement of the present invention is that the optical waveguide can be prepared from porous polymeric or ceramic materials, thereby allowing diffusion of the analyte to a fluorophore contained within the waveguide. In one embodiment, light propagates at an angle to the waveguide. Light measuring components such as a series of light-sensitive photodiodes or a single charge-coupled device camera are used to receive the signal from the waveguide sensor. The light-induced fluorescence is modified by the optical waveguide. The waveguide reflects part of the incoming light at the angle of incidence. Part of the light entering the waveguide excites fluorescence of the fluorophore trapped within the waveguide or deposited on the waveguide. Some fluorescence is trapped in a guided optical mode within the waveguide, and some fluorescent light is reradiated from the waveguide structure. A photodetector is positioned near the waveguide to allow only a restricted field of view of light coming from the waveguide or from the material deposited on the waveguide. Light detected from the waveguide structure contains information concerning the state of the fluorophore which, in turn, contains information about the presence of the analyte.
Multiple analytes may be placed in the optical waveguide or above the optical waveguide through a wide range of techniques. Examples of methods used to produce optical waveguide structures, such that multiple waveguide structures (each containing a different fluorophore) can be deposited on a single sensor element, include but are not limited to the following approaches.
Free standing polymer materials and glass materials can be overlaid with a polymer or ceramic material of refractive index such that an optical waveguide is formed. As an example, polyimide can be deposited on soda-lime glass by following the procedure outlined below. The polyimide films are prepared by spin-coating a solution of polyimide in butyrolactone (Probimide 414, OCG Microelectronic Materials, Inc.) along with an adhesion promoter onto clean glass slides to form a waveguide that is approximately five microns thick. The waveguide structure is baked at approximately 240 degrees Centigrade under a nitrogen atmosphere. The polyimide to exposed to ultraviolet light at 365 nm. A fluorophore is then entrained in the polymer by dye diffusion. Next, the polyimide/dye probe is exposed to ultraviolet light at 365 nm wavelength and approximately 0.75 Joule per square centimeter light energy.
Optical waveguides can also be prepared by laser ablation of aluminum in an oxidizing environment to provide a porous ceramic waveguide structure. Fluorophores are deposited onto the waveguide structure by solution-based procedures. For example, a fluorophore-containing waveguide, such as nile blue A perchlorate in polyimide (Probimide 414, OCG Microelectronic Materials, Inc.), can be coated with oxazine 720 or oxazine 750 in nafion. Nafion perfluorinated ion-exchange powder is available as a 5% solution in Methanol (Aldrich 27,470-4) and can be used directly as received from Aldrich after adding an appropriate quantity of methanol to reach the desired polymer concentration. A 0.3% nafion solution in methanol together with oxazine 720 is optimal for sensing dimethyl methyl phosphonate (DMMP). Layers of oxazine 720/nafion or oxazine 750/nafion can be formed by placing 1.5-2.0 ml of solution on a previously prepared polyimide film. By following that procedure, a fluorophore can be deposited over a waveguide structure, which waveguide structure itself contains another fluorophore. Patterns of fluorophores are produced by dicing the optical waveguide structures fabricated with a range of polymer/dye combinations as the outer coating and adhering those sensor components in a predetermined pattern for sensor operation. The dye/polymer coatings can also be prepared by adhering a wire mesh, a laser-cut array of cells, or any other means of partitioning the surface coating to the waveguide structure, and then filling in the cells using an ink-jet printer, a capillary feed array or other fluid moving apparatus. The array of fluorophores can also be produced by microlithographically producing cells in the waveguide structure or in a layer adhered to the waveguide structure. The optical waveguides and the coatings can be prepared through sol-gel methods of deposition, solvent methods of polymer deposition, and methods involving ablation of a material forming a waveguide structure. In addition, the waveguide can be produced from a combination of deposited sol-gel and polymer sources.
The patterned waveguide structure is then illuminated either by a steady light source providing multiple spots of illumination or by moving the waveguide with respect to the optical source to illuminate one section of the patterned waveguide at a time. In one configuration of the proposed sensor, a fanout grating is used to produce multiple spots after illumination by a laser beam. In a second configuration, a holographic optical element is used to produce multiple spots.
Remote operation of the present invention can be achieved by using optical fibers. The signal from the optical source is guided to the optical waveguide by an optical fiber, and the fluorescent signal from the waveguide structure is detected using one or more optical fibers.
A preferred embodiment of the present invention includes electronically or piezoelectrically modulating the position of the excitation source beam on the optical waveguide array. Electronic modulation of beam position is accomplished using an electroptic material such as lithium niobate or a ferroelectric liquid crystal that exhibits a change in refractive index because of an applied voltage to steer the excitation beam from one fluorophore to another on the optical waveguide surface. In that manner, changes in fluorescence from multiple fluorophores or fluorophores embedded in differing responsive materials are monitored and summed to provide a total instrument response. A synchronous detector can be used to determine differences in phase and amplitude of fluorescence originating from different sensors on the waveguide structure. Along with various synchronous detection circuits, other techniques known in the area of modulation spectroscopy can be used to extract signals from noise.
The optical chemical sensor of the invention uses a multiplicity of fluorescence data to provide information on the identity and concentration of a chemical analyte in the presence of interferents. The preferred optical chemical sensor is based upon an optical waveguide produced by deposition of multiple layers of solvent-deposited polymers, each containing fluorophores, or by multiple layers of sol-gel deposited ceramic layers, each layer containing more or less fluorophore sensor material, or other optical waveguide structures that are excited by a light source at an angle to the waveguide surface. Fluorescence is detected either at a fixed angle to the waveguide surface or through a plurality of angles with respect to the waveguide surface. It is noted that the fluorophores contained in the optical waveguide constitute a resonator structure such that the fluorescence from within the cavity formed by the optical waveguide is enhanced with respect to a fluorophore outside the cavity. Similarly, the effect of the optical waveguide on a fluorophore deposited within the evanescent field of the waveguide is seen as an enhancement of interaction between the cavity and waveguide structures.
Excitation of fluorescence in the presence of the optical waveguide structure provides an enhancement of the optical signal derived from the sensor and allows the sensor to operate without direct coupling to each of the waveguide structures exciting the range of fluorophores necessary for analyte detection. When oxazine 720 in nafion is deposited on a glass optical waveguide structure having a polyimide film, the fluorescence signal is increased by almost a factor of ten over the signal measured when oxazine 720 is deposited over glass alone. It is noted that this sensor responds significantly to the presence of water vapor. Use of oxazine 750 instead of oxazine 720 provides a sensor with much less response in the presence of water vapor. Thus, a sensor containing oxazine 720 and oxazine 750 allows for a measure of water vapor concentration.
One preferred optical chemical sensor contains a multiplicity of receptors positioned as to form an array. An optical sensor according to the invention detects changes in fluorescence amplitude, frequency, decay time, polarization, saturation intensity and stability with temperature. A pump-probe approach may also be used to provide additional data from each element of the fluorophore array.
In a preferred optical chemical sensor, the light illuminating the optical waveguide is generated by a semiconductor laser diode. In the oxazine 720/nafion/polyimide system, the fluorescence excited by a laser emitting at 633 nm-650 nm can be used to detect the presence of DMMP, ammonia or water. Light entering the sensor structure is reflected from the optical waveguide, from partial mirrors deposited at the sensor surface, or from disturbed Bragg reflectors produced in the body of the waveguide or at the edges of the waveguide. The light passes through the fluorophore contained within the body of the sensor structure or interacts with a fluorophore deposited at the surface of the sensor structure. The output optical signal from that sensor body is adapted for use with optical fiber transmission.
The invention provides an optical sensor for identifying and measuring concentrations of chemical analytes in gaseous or liquid phase. The sensor relies on the change in fluorescence emitted from fluorophores incorporated in an optical waveguide or on top of an optical waveguide after exposure to the analyte of interest. The optical waveguide is produced by deposition of multiple layers of polymeric or ceramic materials, such that the refractive indexes of a guiding layer and cladding regions are controllable. By selecting polymeric and ceramic materials with sufficient porosity or diffusional characteristics and by allowing the entire structure to be diffusionally thin to the analyte of interest, changes within an optical cavity produced by interaction with fluorophoric sensor materials can be monitored. Since the waveguide structure is itself seen as an optical cavity, accessibility without direct optical coupling to each sensor component allows rapid evaluation of a wide range of analytes through chemometric methods of analysis. The change in fluorescence from each fluorophore incorporated within or on the optical waveguide is summed as a vector response and evaluated using digital signal processing techniques. This invention is useful in measuring the concentration of gaseous pollutants, toxic chemicals or process products present about the sensor.
The present invention is an improvement over existing sensor instruments. The fluorophore is contained in the porous optical waveguide, in an optical resonator structure, on top of a porous optical waveguide, or on top of an optical resonator structure. That improvement enhances the fluorescence effect. Additionally, the improvements, coupled with the positioning of a multiplicity of receptors in or on the patterned waveguide or patterned optical cavity, eliminates the need for prism, grating or end-fire coupling to the waveguide or cavity and allows modulation of the excitation beam position to gather precise data on differences in fluorescence of an array of fluorophores in the presence of an analyte. Also, by using and summing a multiplicity of fluorescent data, the present invention has greater specificity, decreased noise effects and higher accuracy.
These and further and other objects and features of the invention are apparent in the disclosure, which includes the above and ongoing written specification, with the claims and the drawings.
FIG. 1 is a schematic illustration of a fluorescent waveguide optical sensor in which the waveguide forms an optical cavity and light excitation is at an angle to the waveguide.
FIG. 2 is a schematic illustration of a fluorescent waveguide optical sensor having a fluorophore-containing coating layer applied to the upper surface of the waveguide.
FIG. 3 schematically shows the use of a moving mirror to modulate the position of an excitation beam over a structure produced by depositing a chemically sensitive coating over an optical waveguide containing fluorophores.
FIG. 4 schematically shows a coated optical waveguide having a plurality of regions with fluorophores and hosts and an optical array detector to monitor the fluorescence from each section of the coating.
FIG. 5 schematically shows an array of fluorophore/host regions contained in a coating over an optical waveguide configured as an optical cavity. Fluorescence is detected by a photodetector array.
FIG. 6 is an enlarged schematic detail from FIG. 5.
FIG. 7 schematically shows selectively depositing a range of fluorophores and hosts on an optical waveguide structure.
FIG. 8 shows an alternate embodiment of chemical sensing using optical fibers to deliver light and carry away the signal.
FIG. 9 shows an optical waveguide that uses an optical cavity having dielectric mirrors to increase cavity resonance quality.
Referring to the drawings and initially to FIG. 1, an optical sensor 1 identifies and measures concentrations of chemical analytes in gaseous or liquid phases. The optical sensor 1 includes an optical waveguide 3, a light source 5 and a detector 7. FIG. 1 shows one embodiment of the present invention. The optical waveguide 3 has a substrate layer 9 and an overlying layer 11. Possible materials for the substrate layer 9 include polymer and glass. The overlying layer 11 is a polymer or ceramic material having a refractive index such that an optical waveguide is formed. The overlying layer 11 contains fluorophores 13. In one embodiment the overlying layer 11 is porous, thereby forming a porous optical waveguide 3. One possible porous overlying layer 11 is a polyimide layer. When a porous optical waveguide 3 is created, fluorophores 13 are deposited in the overlying layer 11. Multiple fluorophore regions can be incorporated.
As shown in FIG. 1, a light source 5 illuminates with wave energy 6 the porous optical waveguide 3 containing the fluorophores 13 at an angle. Fluorescence is generated within the waveguide 3. The fluorescence is dependent on the interaction of the fluorophores 13 in the overlying layer 11 of the waveguide 3 with a chemical analyte. A detector 7 positioned near the waveguide 3 detects the fluorescence 8 from the optical waveguide 3. Reflected light 10 from the source 5 is not detected.
FIG. 2 shows another embodiment of the present invention having an optical waveguide 3 with an overlying layer 11 that contains fluorophores. A thin coating 29 containing fluorophores is applied to the upper surface 33 of the layer 11 of the optical waveguide 3. Light 6 emitted from a light source 5 illuminates the optical waveguide 3, thereby exciting the fluorophores contained in the overlying layer 11 of the waveguide 3. Light emitted from those fluorophores causes the fluorescent materials in the coating layer 29 to fluoresce. The fluorescence from the material in the coating layer 29 is dependent on the interaction of the fluorophores in the coating layer 29 with a chemical analyte. A detector 43 positioned near the waveguide 3 detects the fluorescent signal 37. Light detected from the waveguide contains information concerning the states of the fluorophores which, in turn, contain information about the presence of the analyte.
As shown in FIG. 2, fluorescence emitted from the optical waveguide 3 interacts with fluorophores or absorbers present in the coating layer 29 and exhibits an angular dependence in emission intensity. Some incoming light is reflected 39 at the angle of incidence and is not detected. Some light is re-emitted and is blocked by an optical filter 41 designed to separate light at the excitation wavelength from light 37 emitted as fluorescence. An angle-resolvable photodetector 43 is used to determine fluorescence amplitude.
FIGS. 1 and 2 show methods of excitation and detection of the present invention. Light 6 from a light source 5, which may be a semiconductor diode laser, a light-emitting diode, or an optical lamp, impinges upon an optical waveguide 3, thereby exciting a fluorescent material or mix of fluorescent material contained within the waveguide or in the evanescent field of the waveguide. Where the waveguide forms an optical cavity, the fluorescence is preferentially emitted in a given direction and may be amplified or quenched depending upon the available modes of the waveguide. Inserting a polarizer between the fluorescence signal, the optical filter and the photodetector allows the instrument to monitor changes in fluorescence resulting from waveguide response to a chemical analyte.
Patterns of fluorophores can be produced in the waveguide or in the thin coating layer covering the upper surface of the waveguide. The patterned waveguide structure is illuminated through the use of a steady light source providing multiple spots of illumination, through movement of the waveguide with respect to the optical source to illuminate one section of the patterned waveguide at a time, or through other methods of lights modulation.
FIG. 3 shows a horizontal optical waveguide 3 coated with several regions 53 of differing fluorophores in differing host materials. In one embodiment, the position of the beam 55 is modulated by a movable mirror 57. The mirror 57 directs the beam 55 from position 59 to position 61 or position 63. Fluorescent signals, depicted by 65, 67 and 69, are generated and detected through optical filter 71 by photodetector 73. A piezoelectric mover 75 fixed on a base 76 alters the angle of fluorescence detection for each position of the pump beam. Photodetector 77 monitors the reflectance of the surfaces at position 59, position 61 and position 63 and provides an indication of changes in absorbance with time. Fluorescence and reflectance/absorbance data can be advantageously used in analyte detection. In one embodiment, signals 63, 67 and 69 at angles away from the specular reflection maximum are detected by a pair of photodetectors such that one half of the signal passes an optical filter 71 to remove light at the excitation wavelength and the other half of the signal removes light at any wavelength other than the excitation wavelength. That allows for the simultaneous detection of fluorescence and scattered light from the instrument surface. Additional information on fluorescence characteristics is provided by modulating the angle of the waveguide 3 to the incident beam, by modulating the angle of acceptance of the photodiode 77, or by using an array detector to quantify the maximum angle of fluorescence.
FIG. 4 shows one embodiment of the present invention wherein a multiplicity of fluorophore/host regions 81, 82, 84, 86 are excited by an excitation light source 5, such as a stationary pump beam. The fluorescent signals 85 are collected and imaged by a lens 87, are passed through an optical filter 89, and are directed onto a group of photodetectors 91. The use of individual photodetectors 93, 95, 97, 99 provides for evaluation of the fluorescence decay of fluorescent signals 101, 103, 105, 107 from each region 81, 82, 84, 86. To evaluate the fluorescence decay, the excitation light source 83 is modulated from 20 Khz to 100 MHz. The phase delay through each fluorophore/host is related to the relative fluorescence decay of each fluorophore/host. The decay is measured using phase-sensitive detectors operating on the electronic signals produced by each photodiode.
FIG. 5 expands on the embodiment of the present invention shown in FIG. 4. An excitation beam 111 is converted to a multiplicity of beams using a beam converter 113, such as a fanout grating, an holographic optical element, a series of beamsplitters, or a series of beamsplitting optical couplers. Multiple beams 115 are focused onto the coating layer 29 of the optical waveguide 3 by a lens 121. The resulting fluorescent signals 123 are focused through a lens 117 and a filter 119 on a detector 125, such as a plurality of photodetectors, a photodetector array, or a camera. Detector 125 can be an intensified diode array or an intensified charge coupled device camera. The excitation beam is modulated at a frequency from 20 KHz to 100 MHz. The image intensifier is modulated at the same frequency or at a range of offset frequencies to allow for detection of regions of varying fluorescence decay across the waveguide structure.
FIG. 6 shows a detail of FIG. 5. Multiple sections 127, 128, 129, 130, 131, 132 are positioned in the coating layer 29 covering the upper surface of the optical waveguide 3. Each section contains a different fluorophore/host combination. When excited by beams 111 from the light source, fluorescence signals 123 are emitted separately from each section 127, 128, 129, 130, 131. The signals 123 are monitored and differentiated to provide distinct responses or summed to provide an overall response.
In preferred embodiments of the present invention, patterns of fluorophores are produced in the waveguide or in the coating layer. FIG. 7 shows one embodiment wherein a patterned coating layer 29 is prepared using a laser-cut form 143 adhered to the waveguide structure 3. The form 143 permits the deposition of multiple fluorophore/host regions 147 in the cells cut from the form 143. When the form 143 is brazed onto the coating layer 29 of the waveguide 3, the regions 147 are filled using an hydraulic array, an ink jet printer, or other methods of sol-gel transport.
FIG. 8 shows another embodiment of the present invention The sensor body 151 is comprised of an optical waveguide 153 acting as an optical cavity. The waveguide 153 located on substrate 165 is either coated with a fluorophore/host combination 164 or surrounded by dielectric or metallic partial mirrors prior to coating. External mirrors 155 are be used to direct the light through the waveguide 153. Light enters the waveguide 3 through an optical fiber 157 that is optically coupled to the waveguide 153 by an input coupling port 159. Light coupled into the waveguide 153 is reflected multiple times. The fluorescence signal leaves the waveguide 153 at output port 161 through an optical fiber 163. The mirrors control the reflection of the light input and the fluorescence signal output thereby allowing the fluorescence signal to be separated from reflected or scattered light. That occurs as a result of the angular dependence of fluorescence within the structure. The light energizations and the fluorescence signal detections may be modulated or filtered to insure against erroneous detection of the input as an output signal.
FIG. 9 shows an embodiment of the present invention having multiple layers 171 deposited on the top surface 173 and the bottom surface 175 of the waveguide 3. Each layer 171 is a pair of dielectrics. In one embodiment, the sensor is produced by deposition of multiple layers 171 of solvent-deposited polymers, each containing fluorophores. In a second embodiment, the sensor is produced by deposition of multiple layers of sol-gel ceramics, each layer containing more or less fluorophore sensor material. A substrate 9 is positioned below the bottom surface 181 of the bottom layer and a coating layer 29 is positioned above the top surface 185 of the top layer. The dielectric layers function as dielectric mirrors and provide for vertical resonance. The sensor is designed to transmit the incident beam and reflect the fluorescence.
While the invention has been described with reference to specific embodiments, modifications and variations of the invention may be constructed without departing from the scope of the invention, which is defined in the following claims.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US4050895 *||Sep 17, 1976||Sep 27, 1977||Monsanto Research Corporation||Optical analytical device, waveguide and method|
|US4548907 *||Sep 14, 1983||Oct 22, 1985||Allied Corporation||Fluorescent fluid determination method and apparatus|
|US4582809 *||Aug 9, 1982||Apr 15, 1986||Myron J. Block||Apparatus including optical fiber for fluorescence immunoassay|
|US4654532 *||Sep 9, 1985||Mar 31, 1987||Ord, Inc.||Apparatus for improving the numerical aperture at the input of a fiber optics device|
|US4803049 *||Dec 12, 1984||Feb 7, 1989||The Regents Of The University Of California||pH-sensitive optrode|
|US4815843 *||May 29, 1986||Mar 28, 1989||Oerlikon-Buhrle Holding Ag||Optical sensor for selective detection of substances and/or for the detection of refractive index changes in gaseous, liquid, solid and porous samples|
|US4818710 *||Dec 6, 1985||Apr 4, 1989||Prutec Limited||Method for optically ascertaining parameters of species in a liquid analyte|
|US4844613 *||Nov 2, 1987||Jul 4, 1989||Stc Plc||Optical surface plasmon sensor device|
|US4877747 *||Apr 4, 1986||Oct 31, 1989||Plessey Overseas Limited||Optical assay: method and apparatus|
|US4880752 *||Feb 24, 1989||Nov 14, 1989||Ciba Corning Diagnostics Corp.||Dielectric waveguide sensors and their use in immunoassays|
|US4889690 *||May 7, 1987||Dec 26, 1989||Max Planck Gesellschaft||Sensor for measuring physical parameters of concentration of particles|
|US4929561 *||Aug 8, 1985||May 29, 1990||Regents Of The University Of California||Absorption-emission optrode and methods of use thereof|
|US4980278 *||Apr 24, 1989||Dec 25, 1990||Olympus Optical Co., Ltd.||Method of effecting immunological analysis and apparatus for carrying out the same|
|US5019350 *||Feb 13, 1986||May 28, 1991||Pfizer Hospital Products, Inc.||Fluorescent polymers|
|US5045282 *||Oct 14, 1988||Sep 3, 1991||Optical Chemical Tech. Ltd.||Optical fiber sensing device for analysis|
|US5093266 *||Feb 27, 1989||Mar 3, 1992||Shiley Inc.||Sensor system|
|US5094517 *||Aug 10, 1990||Mar 10, 1992||Hoechst Aktiengesellschaft||Polyimide waveguides as optical sensors|
|US5094959 *||Apr 26, 1989||Mar 10, 1992||Foxs Labs||Method and material for measurement of oxygen concentration|
|US5096671 *||Mar 15, 1989||Mar 17, 1992||Cordis Corporation||Fiber optic chemical sensors incorporating electrostatic coupling|
|US5114676 *||Jul 28, 1989||May 19, 1992||Avl Ag||Optical sensor for determining at least one parameter in a liquid or gaseous sample|
|US5120131 *||Feb 14, 1988||Jun 9, 1992||Walter Lukosz||Method and apparatus for selecting detection of changes in samples by integrated optical interference|
|US5127405 *||Feb 16, 1990||Jul 7, 1992||The Boc Group, Inc.||Biomedical fiber optic probe with frequency domain signal processing|
|US5154890 *||Nov 7, 1990||Oct 13, 1992||Hewlett-Packard Company||Fiber optic potassium ion sensor|
|US5156972 *||Sep 5, 1990||Oct 20, 1992||The State Of Israel, Atomic Energy Commission, Soreq Nuclear Research Center||Analyte specific chemical sensor with a ligand and an analogue bound on the sensing surface|
|US5194393 *||Nov 8, 1990||Mar 16, 1993||Bayar Aktiengesellschaft||Optical biosensor and method of use|
|US5196709 *||May 3, 1991||Mar 23, 1993||University Of Maryland Systems||Fluorometry method and apparatus using a semiconductor laser diode as a light source|
|US5212099 *||Jan 18, 1991||May 18, 1993||Eastman Kodak Company||Method and apparatus for optically measuring concentration of an analyte|
|US5227134 *||Jul 29, 1991||Jul 13, 1993||Jiri Janata||Dynamic immunochemical and like chemical species sensor apparatus and method|
|US5237631 *||Mar 31, 1992||Aug 17, 1993||Moshe Gavish||Method for the manufacture of a fluorescent chemical sensor for determining the concentration of gases, vapors or dissolved gases in a sample|
|US5302349 *||Mar 6, 1990||Apr 12, 1994||Diatron Corporation||Transient-state luminescence assay apparatus|
|US5308581 *||Dec 12, 1991||May 3, 1994||Avl Medical Instruments Ag||Substance of an optical fluorescence measuring arrangement for measuring the pH of a sample and optical sensor with such an indicator substance|
|US5315672 *||Sep 23, 1991||May 24, 1994||Texas Instruments Incorporated||Fiber optic chemical sensor|
|US5324635 *||Aug 24, 1989||Jun 28, 1994||Hitcahi, Ltd.||Method and apparatus for automatic measurement of fluorescence|
|US5344784 *||Nov 28, 1989||Sep 6, 1994||Applied Research Systems Ars Holding N.V.||Fluorescent assay and sensor therefor|
|US5447845 *||Dec 6, 1994||Sep 5, 1995||E. I. Du Pont De Nemours And Company||Analyte-responsive KTP composition and method|
|USRE31879 *||Jul 29, 1982||May 7, 1985||Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V.||Method and arrangement for measuring the concentration of gases|
|1||Feddersen et al., "Digital Parallel Acquisition . . . ", Review Of Scientific Instruments, vol. 60, No. 9, pp. 2929-2936 (1989).|
|2||*||Feddersen et al., Digital Parallel Acquisition . . . , Review Of Scientific Instruments, vol. 60, No. 9, pp. 2929 2936 (1989).|
|3||Haruvy et al., "Sol-Gel Preparation of Optically-Clear Supported Thin Film Glasses . . . ", Supramolecular Architecture, pp. 405-424 (1992).|
|4||Haruvy et al., "Supported Sol-Gel Thin-Film Glasses . . . ", Submolecular Glass Chemistry & Physics, SPIE vol. 1590, pp. 59-70 (1991).|
|5||*||Haruvy et al., Sol Gel Preparation of Optically Clear Supported Thin Film Glasses . . . , Supramolecular Architecture, pp. 405 424 (1992).|
|6||*||Haruvy et al., Supported Sol Gel Thin Film Glasses . . . , Submolecular Glass Chemistry & Physics, SPIE vol. 1590, pp. 59 70 (1991).|
|7||Janans et al., "Integrated Planar Optical Imaging System . . . ", Optics Letters, vol. 18, No. 19, pp. 1594-1596 (1993).|
|8||*||Janans et al., Integrated Planar Optical Imaging System . . . , Optics Letters, vol. 18, No. 19, pp. 1594 1596 (1993).|
|9||*||Levy, D., Journal Of Non Crystalline Solids, vol. 147 148, pp. 508 517 (1992).|
|10||Levy, D., Journal Of Non-Crystalline Solids, vol. 147-148, pp. 508-517 (1992).|
|11||*||Reisfeld and Jorgensen, Structure And Bonding, pp. 208 256 (1992).|
|12||Reisfeld and Jorgensen, Structure And Bonding, pp. 208-256 (1992).|
|13||Tanguay, "Integrated Optical Information Processing", AFOSR-85-0312, AD-A201 016, Air Force Office Of Scientific Research (1988).|
|14||*||Tanguay, Integrated Optical Information Processing , AFOSR 85 0312, AD A201 016, Air Force Office Of Scientific Research (1988).|
|15||*||Zusman et al., Journal Of Non Crystalline Solids, vol. 122, pp. 107 109 (1990).|
|16||Zusman et al., Journal Of Non-Crystalline Solids, vol. 122, pp. 107-109 (1990).|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US5945343 *||Aug 5, 1997||Aug 31, 1999||Bayer Corporation||Fluorescent polymeric sensor for the detection of urea|
|US5958786 *||Aug 5, 1997||Sep 28, 1999||Bayer Corporation||Fluorescent polymeric sensor for the detection of creatinine|
|US5991082 *||Feb 21, 1997||Nov 23, 1999||Nikon Corporation||Lens system with multiple focal lines|
|US6013529 *||Aug 5, 1997||Jan 11, 2000||Bayer Corporation||Hydrophobic fluorescent polymer membrane for the detection of ammonia|
|US6016689 *||Nov 18, 1996||Jan 25, 2000||The Research Foundation Of Suny At Buffalo||Aerosol-generated sol-gel derived thin films and applications thereof|
|US6107099 *||Dec 6, 1999||Aug 22, 2000||Bayer Corporation||Hydrophobic fluorescent polymer membrane for the detection of ammonia|
|US6300638||Nov 12, 1998||Oct 9, 2001||Calspan Srl Corporation||Modular probe for total internal reflection fluorescence spectroscopy|
|US6303937||Feb 27, 1998||Oct 16, 2001||Eastman Kodak Company||Ceramic calibration filter|
|US6320887||Aug 29, 2000||Nov 20, 2001||Eastman Kodak Company||Ceramic calibration filter|
|US6331438 *||Nov 24, 1999||Dec 18, 2001||Iowa State University Research Foundation, Inc.||Optical sensors and multisensor arrays containing thin film electroluminescent devices|
|US6429022||Feb 22, 2000||Aug 6, 2002||Csem Centre Suisse D'electronique Et De Microtechnique Sa||Integrated-optical sensor and method for integrated-optically sensing a substance|
|US6594414 *||Jul 25, 2001||Jul 15, 2003||Motorola, Inc.||Structure and method of fabrication for an optical switch|
|US6717966||Aug 30, 2001||Apr 6, 2004||Eastman Kodak Company||Calibration focus position|
|US6785433||Aug 9, 2001||Aug 31, 2004||Artificial Sensing Instruments Asi Ag||Waveguide grid array and optical measurement arrangement|
|US6855556||Jan 4, 2002||Feb 15, 2005||Becton, Dickinson And Company||Binding protein as biosensors|
|US6903815||Nov 22, 2002||Jun 7, 2005||Kabushiki Kaisha Toshiba||Optical waveguide sensor, device, system and method for glucose measurement|
|US7013072 *||Nov 22, 2004||Mar 14, 2006||Kabushiki Kaisha Toshiba||Optical device and optical module|
|US7027163||Jan 24, 2003||Apr 11, 2006||General Dynamics Advanced Information Systems, Inc.||Grating sensor|
|US7054514||Feb 7, 2005||May 30, 2006||Kabushiki Kaisha Toshiba||Optical waveguide sensor, device, system and method for glucose measurement|
|US7158224||Jun 25, 2001||Jan 2, 2007||Affymetrix, Inc.||Optically active substrates|
|US7445938||Nov 18, 2004||Nov 4, 2008||General Dynamics Advanced Information Systems, Inc.||System and method for detecting presence of analytes using gratings|
|US7473906||Apr 25, 2006||Jan 6, 2009||Claudio Oliveira Egalon||Reversible, low cost, distributed optical fiber sensor with high spatial resolution|
|US7496245 *||Aug 20, 2004||Feb 24, 2009||Research International, Inc.||Misalignment compensating optical sensor and method|
|US7537734 *||Oct 10, 2001||May 26, 2009||University Of Utah Research Foundation||Integrated optic waveguide immunosensor|
|US7627201||Jul 6, 2004||Dec 1, 2009||Artificial Sensing Instruments Asi Ag||Waveguide grating structure and optical measurement arrangement|
|US7629172||Sep 27, 2004||Dec 8, 2009||Becton, Dickinson And Company||Entrapped binding protein as biosensors|
|US7670564 *||Jan 28, 2005||Mar 2, 2010||Hitachi High-Technologies Corporation||Liquid dispensing apparatus, automatic analyzer using same, and liquid surface detecting apparatus|
|US7741131 *||May 25, 2007||Jun 22, 2010||Electro Scientific Industries, Inc.||Laser processing of light reflective multilayer target structure|
|US7951583||Mar 8, 2007||May 31, 2011||Plc Diagnostics, Inc.||Optical scanning system|
|US7951605||Jun 7, 2005||May 31, 2011||Becton, Dickinson And Company||Multianalyte sensor|
|US8153066 *||Apr 14, 2005||Apr 10, 2012||Genewave||Device for supporting chromophore elements|
|US8182748 *||Mar 7, 2008||May 22, 2012||Janesko Oy||Method and arrangement of measuring acidity or other chemical or physical property of a gas|
|US8187866||May 17, 2011||May 29, 2012||Plc Diagnostics, Inc.||Optical scanning system|
|US8288157||Sep 12, 2008||Oct 16, 2012||Plc Diagnostics, Inc.||Waveguide-based optical scanning systems|
|US8463083||Jan 30, 2010||Jun 11, 2013||Claudio Oliveira Egalon||Side illuminated multi point multi parameter optical fiber sensor|
|US8675199||Apr 28, 2010||Mar 18, 2014||Plc Diagnostics, Inc.||Waveguide-based detection system with scanning light source|
|US8747751||Jun 10, 2009||Jun 10, 2014||Plc Diagnostics, Inc.||System and method for nucleic acids sequencing by phased synthesis|
|US8831709||Sep 26, 2005||Sep 9, 2014||Softscan Healthcare Group Ltd.||Method for 3-dimensional fluorescence tomographic imaging|
|US8909004||May 11, 2013||Dec 9, 2014||Claudio Oliveira Egalon||Side illuminated multi point multi parameter|
|US8992836||Nov 16, 2009||Mar 31, 2015||Cornell University||Cavity-enhanced on-chip absorption spectroscopy|
|US9170201||Jul 1, 2013||Oct 27, 2015||Artificial Sensing Instrument Asi Ag||Waveguide grating structure and optical measurement arrangement|
|US9341573||Oct 21, 2015||May 17, 2016||Artificial Sensing Instruments Asi Ag||Waveguide grating structure and optical measurement arrangement|
|US9423397||Feb 28, 2014||Aug 23, 2016||Indx Lifecare, Inc.||Waveguide-based detection system with scanning light source|
|US9528939||Sep 13, 2012||Dec 27, 2016||Indx Lifecare, Inc.||Waveguide-based optical scanning systems|
|US9562847||Apr 3, 2009||Feb 7, 2017||Asmag-Holding Gmbh||Modular absorption measuring system|
|US9575003 *||Feb 11, 2015||Feb 21, 2017||Fujifilm Corporation||Optical field enhancement device, light measurement apparatus and method|
|US9739709||May 8, 2014||Aug 22, 2017||Colorado State University Research Foundation||Hydrocarbon sensing methods and apparatus|
|US20020034457 *||Oct 10, 2001||Mar 21, 2002||Reichert W. Monty||Integrated optic waveguide immunosensor|
|US20020192680 *||Feb 21, 2002||Dec 19, 2002||Selena Chan||Microcavity biosensor, methods of making, and uses thereof|
|US20020192836 *||Feb 12, 2002||Dec 19, 2002||Calspan Srl Corporation||Detection of chemical agent materials using a sorbent polymer and fluorescent probe|
|US20030133640 *||Aug 9, 2001||Jul 17, 2003||Kurt Tiefenthaler||Waveguide grid array and optical measurement arrangement|
|US20030225322 *||Nov 22, 2002||Dec 4, 2003||Kenichi Uchiyama||Optical waveguide sensor, device, system and method for glucose measurement|
|US20030232427 *||Jun 17, 2003||Dec 18, 2003||Montagu Jean I.||Optically active substrates for examination of biological materials|
|US20040046128 *||Aug 28, 2003||Mar 11, 2004||Andreas Peter Abel||Sensor platform and method for the determination of multiple analytes|
|US20040058385 *||Nov 5, 2001||Mar 25, 2004||Abel Andreas Peter||Kit and method for determining multiple analytes, with provisions for refrencing the density of immobilised recognition elements|
|US20040125370 *||Jun 25, 2001||Jul 1, 2004||Montagu Jean I.||Optically active substrates|
|US20040145752 *||Jan 24, 2003||Jul 29, 2004||David Angeley||Grating sensor|
|US20040247229 *||Jul 6, 2004||Dec 9, 2004||Artificial Sensing Instruments Asi Ag||Waveguide grating structure and optical measurement arrangement|
|US20050042704 *||Sep 27, 2004||Feb 24, 2005||Javier Alarcon||Entrapped binding protein as biosensors|
|US20050068543 *||Nov 18, 2004||Mar 31, 2005||General Dynamics Advanced Information Systems, Inc.||System and method for detecting presence of analytes using gratings|
|US20050089292 *||Nov 22, 2004||Apr 28, 2005||Kabushiki Kaisha Toshiba||Photonic crystal, method of fabricating the same, optical module, and optical system|
|US20050147342 *||Feb 7, 2005||Jul 7, 2005||Kabushiki Kaisha Toshiba||Optical waveguide sensor, device, system and method for glucose measurement|
|US20050201899 *||Apr 14, 2005||Sep 15, 2005||Genewave||Device for supporting chromophore elements|
|US20050221279 *||Apr 4, 2005||Oct 6, 2005||The Regents Of The University Of California||Method for creating chemical sensors using contact-based microdispensing technology|
|US20050242117 *||Jan 28, 2005||Nov 3, 2005||Goro Yoshida||Liquid dispensing apparatus, automatic analyzer using same, and liquid surface detecting apparatus|
|US20060039643 *||Aug 20, 2004||Feb 23, 2006||Saaski Elric W||Misalignment compensating optical sensor and method|
|US20060078908 *||Jun 7, 2005||Apr 13, 2006||Pitner James B||Multianalyte sensor|
|US20060276047 *||Mar 14, 2006||Dec 7, 2006||University Of Rochester||Macroporous silicon microcavity with tunable pore size|
|US20080008625 *||Oct 27, 2005||Jan 10, 2008||Thomas Ross C||Infrared sensor|
|US20080227215 *||Mar 7, 2008||Sep 18, 2008||Janesko Oy||Method and arrangement of measuring acidity for other chemical or physical property of a gas|
|US20080255461 *||Mar 26, 2008||Oct 16, 2008||Robert Weersink||Real-time optical monitoring system and method for thermal therapy treatment|
|US20080260647 *||Sep 26, 2005||Oct 23, 2008||Art, Advanced Research Technologies Inc.||Method for Fluorescence Tomographic Imaging|
|US20080272311 *||Apr 25, 2006||Nov 6, 2008||Claudio Oliveira Egalon||Improved Reversible, low cost, distributed optical fiber sensor with high spatial resolution|
|US20080293166 *||May 25, 2007||Nov 27, 2008||Electro Scientific Industries, Inc.||Laser processing of light reflective multilayer target structure|
|US20090180932 *||Oct 31, 2008||Jul 16, 2009||General Dynamics Advanced Information Systems, Inc.||System and method for detecting presence of analytes using gratings|
|US20100124787 *||Nov 16, 2009||May 20, 2010||Arthur Nitkowski||Cavity-enhanced on-chip absorption spectroscopy|
|US20100202726 *||Jan 30, 2010||Aug 12, 2010||Claudio Oliveira Egalon||Side illuminated multi point multi parameter optical fiber sensor|
|US20100239465 *||May 8, 2007||Sep 23, 2010||Eads Deutschland Gmbh||Fluorescence Sensor for Detecting Gas Compositions|
|US20110141475 *||Apr 3, 2009||Jun 16, 2011||Nanoident Technologies Ag||Modular Absorption Measuring System|
|US20150055133 *||Nov 4, 2014||Feb 26, 2015||Claudio Oliveira Egalon||Side illuminated multi point multi parameter optical fiber sensor|
|US20150153284 *||Feb 11, 2015||Jun 4, 2015||Fujifilm Corporation||Optical field enhancement device, light measurement apparatus and method|
|USRE43937||Jan 6, 2011||Jan 22, 2013||Claudio Oliveira Egalon||Reversible, low cost, distributed optical fiber sensor with high spatial resolution|
|USRE46165 *||Jul 14, 2015||Sep 27, 2016||Genewave||Device for supporting chromophore elements|
|CN103289678A *||May 28, 2013||Sep 11, 2013||宁夏医科大学||MLDH (magnetic layered double hydroxides)-Fluorescein intercalation assembled type fluorescent probe|
|CN103289678B *||May 28, 2013||Sep 9, 2015||宁夏医科大学||MLDH-Fluorescein插层组装型荧光探针|
|DE10101576B4 *||Jan 15, 2001||Feb 18, 2016||Presens Precision Sensing Gmbh||Optischer Sensor und Sensorfeld|
|EP0793090A1 *||Feb 12, 1997||Sep 3, 1997||AVL Medical Instruments AG||Measuring system with probe carrier transparent for excitation and measurement beam|
|EP0979994A2 *||Aug 11, 1999||Feb 16, 2000||Instituto Elettrotecnico Nazionale Galileo Ferraris||Porous material optical gas sensing device|
|EP0979994A3 *||Aug 11, 1999||Mar 29, 2000||Instituto Elettrotecnico Nazionale Galileo Ferraris||Porous material optical gas sensing device|
|EP1031828A1 *||Feb 25, 1999||Aug 30, 2000||C.S.E.M. Centre Suisse D'electronique Et De Microtechnique Sa||Integrated-optical sensor and method for integrated-optically sensing a substance|
|EP1965197A1 *||Feb 20, 2008||Sep 3, 2008||Honeywell International Inc.||Appparatus and method for chemical sensing|
|WO2002012865A1 *||Aug 9, 2001||Feb 14, 2002||Artificial Sensing Instruments Asi Ag||Waveguide grid array and optical measurement arrangement|
|WO2002056023A1 *||Jan 15, 2002||Jul 18, 2002||Presens Precision Sensing Gmbh||Optical sensor and sensor array|
|WO2002066965A2 *||Feb 19, 2002||Aug 29, 2002||Scientific Generics Limited||Assay apparatus, assay method and probe array for use in same|
|WO2002066965A3 *||Feb 19, 2002||Feb 13, 2003||Scient Generics Ltd||Assay apparatus, assay method and probe array for use in same|
|WO2006032151A1 *||Sep 26, 2005||Mar 30, 2006||Art, Advanced Research Technologies Inc.||Method for fluorescence tomographic imaging|
|WO2006116590A1 *||Apr 26, 2006||Nov 2, 2006||Claudio Oliveira Egalon||Improved reversible, low cost, distributed optical fiber sensor with high spatial resolution|
|WO2007137550A1 *||May 8, 2007||Dec 6, 2007||Eads Deutschland Gmbh||Fluorescence sensor for detecting gas compositions|
|WO2014182893A1 *||May 8, 2014||Nov 13, 2014||Colorado State University Research Foundation||Hydrocarbon sensing methods and apparatus|
|U.S. Classification||385/12, 422/68.1, 385/130, 385/131, 385/14, 385/37, 250/576, 250/227.11, 250/227.14|
|International Classification||G02B6/02, G01N21/64, G02B6/132, G01N21/77|
|Cooperative Classification||G02B6/02, G01N2021/7793, G01N21/648, G02B6/132, G01N21/7703, G01N21/6428, G01N21/6408|
|European Classification||G02B6/132, G02B6/02, G01N21/77B, G01N21/64H, G01N21/64P8|
|Feb 22, 1995||AS||Assignment|
Owner name: AMERICAN RESEARCH CORPORATION OF VIRGINA, VIRGINIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:GROGER, HOWARD P.;LO, PETER;CHURCHILL, RUSSELL J.;AND OTHERS;REEL/FRAME:007366/0278;SIGNING DATES FROM 19950125 TO 19950215
|Mar 30, 2000||FPAY||Fee payment|
Year of fee payment: 4
|May 19, 2004||FPAY||Fee payment|
Year of fee payment: 8
|May 19, 2008||FPAY||Fee payment|
Year of fee payment: 12